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Deficiency of invariant V alpha 14 natural killer T cells decreases atherosclerosis in LDL receptor null mice.


ABSTRACT:

Aims

CD1d-restricted natural killer T (NKT) cells function by regulating numerous immune responses during innate and adaptive immunity. Depletion of all populations of CD1d-dependent NKT cells has been shown by several groups to reduce atherosclerosis in two different mouse models of the disease. In this study, we determined if removal of a single (V alpha 14) NKT cell population protects mice from the disease.

Methods and results

Targeted deletion of the J alpha 18 gene results in selective depletion of CD1d-dependent V alpha 14 NKT cells in C57BL/6 mice without affecting the population of other NKT, NK, and conventional T cells. Therefore, to study the effect of V alpha 14 NKT cell depletion on the progression of atherosclerosis, we examined the extent of lesion formation using paired littermate LDL receptor null mice that were either +/+ or -/- for the J alpha 18 gene following the feeding of these mice a cholesterol- and fat-enriched diet for 8 weeks. At the end of the study, we found no difference in either serum total- or lipoprotein-cholesterol distributions between groups. However, quantification of atherosclerosis revealed that V alpha 14 NKT cell deficiency significantly decreased lesion size in the aortic root (20-28%) and arch (28-38%) in both genders of mice. By coupling the techniques of laser capture microdissection with quantitative real-time RT-PCR, we found that expression of the proatherogenic cytokine interferon (IFN)-gamma was significantly reduced in lesions from J alpha 18-/- mice.

Conclusion

This study is the first to identify a specific subpopulation of NKT cells that promotes atherosclerosis via a mechanism appearing to involve IFN-gamma expression.

SUBMITTER: Rogers L 

PROVIDER: S-EPMC5439367 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Deficiency of invariant V alpha 14 natural killer T cells decreases atherosclerosis in LDL receptor null mice.

Rogers Leah L   Burchat Sarah S   Gage Jessica J   Hasu Mirela M   Thabet Mohamad M   Willcox Lindsay L   Ramsamy Tanya A TA   Whitman Stewart C SC  

Cardiovascular research 20080110 1


<h4>Aims</h4>CD1d-restricted natural killer T (NKT) cells function by regulating numerous immune responses during innate and adaptive immunity. Depletion of all populations of CD1d-dependent NKT cells has been shown by several groups to reduce atherosclerosis in two different mouse models of the disease. In this study, we determined if removal of a single (V alpha 14) NKT cell population protects mice from the disease.<h4>Methods and results</h4>Targeted deletion of the J alpha 18 gene results i  ...[more]

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